BACKGROUND:The traditional Chinese medicine (TCM) Trichosanthes pericarpium (TP) exerts uniquely therapeutic effect on a TCM syndrome of coronary heart disease, the phlegm turbid obstruction syndrome, the primary characteristic of which is severe lipid metabolism disorder. However, the mechanism underlying the remains elusive. OBJECTIVE:We speculated that protecting heart from damaged by hyperlipidemia via evoking fibroblast growth factor 21 (FGF21) signaling may partly account for above mechanism. METHODS:Rat primary myocardial cells (MCs) was isolated from the heart of neonatal rats, and were exposure to oxidized low density lipoprotein (ox-LDL), together with or without the water fraction (TP-W), the effective constituents of TP. RESULTS:Severe apoptosis was could be observed in MCs exposure to ox-LDL, meanwhile, the level of FGF21 in cells and medium increased significantly; however, the upregulation of βKlotho expression was suppressed dramatically, fibroblast receptor substrate 2α (p-FRS2α) could not be adequately phosphorylated too. In cells incubated with both ox-LDL and TP-W, the expression of FGF21 was accelerated notably; moreover, the level of βKlotho and p-FRS2α was promoted memorably while the apoptosis was reduced signally. CONCLUSIONS:TP-W could rescue the apoptosis stimulated by ox-LDL via activating FGF21 signaling, restoring its sensitivity to FGF21 in MCs.

To systematically deconvolute bioactive components of the n-butanol fraction of Gualou-Xiebai-Banxia decoction (GXB-N) mitigating myocardial ischemia, an integrated drug discovery strategy combining affinity ultrafiltration with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed. This approach was designed to screen specific ligands from the complex matrix that bind to key proteins of the fibroblast growth factor 21 (FGF21) signaling complex, including fibroblast growth factor receptor 1 (FGFR1), βKlotho, and fibroblast growth factor receptor substrate 2α (FRS2α). The thermodynamic stability of identified ligands was evaluated using molecular docking and molecular dynamics simulations, while pharmacological efficacy was validated in an isoproterenol-induced zebrafish model. The screening strategy successfully identified Timosaponin BII as a lead compound with notable binding for the FGFR1/βKlotho-FRS2α complex. In silico simulations demonstrated that Timosaponin BII stably occupies the active pockets of these targets. In vivo assays revealed that Timosaponin BII treatment significantly reversed myocardial ischemia phenotypes, characterized by improved cardiac function and reduced pathological lesions, through the activation of the FGF21 signaling pathway. This study demonstrates the efficacy of the affinity ultrafiltration LC-MS/MS method for clarifying the molecular mechanisms of complex herbal matrices and supports the potential of Timosaponin BII as a therapeutic agent for coronary artery disease.

OBJECTIVES:To investigate the anti-inflammatory mechanism and potential bioactive compounds of the flavonoids of Trichosanthis Fructus (TF) in LPS-induced acute lung injury (ALI) mice. METHODS:The active fraction of TF was screened based on nitric oxide (NO) levels in RAW264.7 cells, and its antioxidant capacity was evaluated in BEAS-2B cells. Balb/c mice were intratracheally instilled with LPS (3 mg/kg), and the levels of Interleukin-1β (IL-1β), IL-6, and Tumor necrosis factor alpha (TNF-α) in serum and lung were measured. The targets of TF intervention in ALI were predicted using Western blotting. The compounds that bind specifically to the targets were identified by affinity ultrafiltration mass spectrometry, and then validated the binding specificity using surface plasmon resonance technology. KEY FINDINGS:The NO level in LPS-induced RAW264.7 was significantly reduced by the ethyl acetate fraction of TF (TF-EA), and the reactive oxygen species level in H2O2-induced BEAS-2B cells was also decreased. Subsequently, TF-EA may significantly improve LPS-induced ALI in mice by EGFR and TLR4-mediated PI3K/Akt signaling pathway. The flavonoids especially rutin, luteolin-7-O-glucoside, apigenin-7-O-glucoside, and diosmetin-7-O-glucoside had better binding with Epidermal growth factor receptor (EGFR) and Toll-like receptor 4 (TLR4). CONCLUSIONS:The TF-EA may reduce the release of inflammatory factors by affecting the PI3K/Akt signaling pathway mediated by EGFR and TLR4.

A renowned traditional Chinese medicine (TCM) classical formula, Gualou-Xiebai-Banxia decoction (GXBD), exhibits unique and significant therapeutic effects in patients with diabetes mellitus complicated by coronary heart disease (DM-CHD). The mechanism underlying its clinical efficacy remains poorly defined. GXBD exerts a potent dual capacity to ameliorate glycolipid metabolic disorders while mitigating MI-induced myocardial injury. This synergistic effect is very similar to the beneficial effects exerted by fibroblast growth factor 21 (FGF21). This study aims to investigate whether GXBD prevents T2DM-CHD from inflicting heart damage and glycolipid metabolic disorders by activating the FGF21/FGF receptor 1 (FGFR1)/βKlotho/fibroblast receptor substrate 2α (FRS2α) pathway. To establish the T2DM-CHD model, SD rat was intraperitoneally injected with streptozocin after high-fat emulsion gavage for twenty-eight days. Then, the coronary artery ligation operation was performed. GXBD was administered intragastrically. Plasma levels of FGF21, myocardial enzymes, blood glucose, and lipid were detected by enzyme-linked immunosorbent assay. Myocardial ischemic size was assessed via triphenyltetrazolium chloride staining, while protein and mRNA expression were analyzed by immunofluorescence, Western blot, and RTPCR. GXBD treatment significantly alleviated myocardial injury and glycolipid metabolic disorders, while reducing circulating and cardiac FGF21 levels in T2DM-CHD rats. Notably, this classical TCM prescription markedly upregulated cardiac βKlotho and Klb mRNA expression, and enhanced the expression and phosphorylation of FRS2α in model rats. In the diabetic heart, AMI fails to effectively activate the FGF21-FRS2α signaling pathway due to insufficient βKlotho upregulation, while GXBD restores FGF21 sensitivity by inducing βKlotho expression, thereby exerting cardioprotective effects. In the diabetic heart, AMI fails to effectively activate the FGF21-FRS2α signaling pathway due to insufficient βKlotho upregulation, while GXBD restores FGF21 sensitivity by inducing βKlotho expression, thereby exerting cardioprotective effects. These findings elucidated a key pathological mechanism in T2DM-CHD and provide mechanistic insights into GXBD's therapeutic efficacy.

This study explored the potential mechanism of Trichosanthes Pericarpium(TP) in the treatment of intermingled phlegm and blood stasis syndrome of coronary heart disease(CAD-TY) through transcriptomics and metabolomics. SD rats were randomly divided into a control group, a model group, a positive drug Salvia miltiorrhiza group, a high-dose TP group, and a low-dose TP group. The CAD-TY model was prepared by using three methods: infusion of high fat emulsion, intraperitoneal injection of streptozotocin, and coronary artery ligation. The activity or content of total cholesterol(TC), triglyceride(TG), low density lipoprotein(LDL), high density lipoprotein(HDL), blood glucose(GLU), creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and troponin I(cTnI) in plasma was detected by enzyme-linked immunosorbent assay and biochemical kit. Transcriptomics and metabolomics techniques were used to detect differentially expressed genes and differential metabolites in heart tissue. Enrichment analyses were conducted through Kyoto Encyclopedia of Genes and Genomes(KEGG). The expressions of key genes and proteins were verified by reverse transcription-quantitative polymerase chain reaction(RT-qPCR) and Western blot. The results showed that compared with the control group, the model group exhibited severe glucolipid metabolism disorder and myocardial infarction. The activity or content of TC, TG, LDL, GLU, CK, CK-MB, and cTnI in plasma was significantly increased, while the content of HDL was significantly decreased. TP intervention could reverse these pathological changes in model rats. A total of 375 potential genes of TP for the treatment of CAD-TY were identified by transcriptomic analysis. These genes were mainly enriched in signal pathways such as adenosine 5'-monophosphate-activated protein kinase(AMPK), forkhead box O(FoxO), and insulin resistance. Metabolomic analysis showed that TP could reverse the content of 74 metabolites in CAD-TY rats, mainly including lipid metabolites such as enoylcarnitine, corticosterone, and other endogenous components. The metabolites were enriched in metabolic pathways related to glycolipid metabolism, including steroid hormone biosynthesis, lipolysis, and glycolysis/gluconeogenesis. Based on the analysis of transcriptome and metabolome results, the key targets enriched in the AMPK signaling pathway were verified. The results of RT-qPCR detection showed that compared with those of the control group, the expressions of key genes sestrin 1(SESN1), AMP-activated protein kinase catalytic subunit alpha-2(PRKAA2), peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PPARGC1A), insulin receptor(INSR), FoxO3, and Unc-51 like kinase 1(ULK1) mRNAs were significantly decreased in the model group(P<0.01). Compared with those of the model group, the mRNA expressions of the above genes in the hearts of rats in the TP group were significantly increased(P<0.01). The results of Western blot showed that TP could significantly increase the expressions of SESN1, PRKAA2, and PPARGC1A proteins(P<0.01). The detection results of RT-qPCR and Western blot were consistent with those of the transcriptomic analysis. The above research results indicate that TP can significantly improve the glycolipid metabolism disorder of CAD-TY rats and thereby has a protective effect on the damaged myocardium. TP may exert a cardiac protective effect on CAD-TY by upregulating the expression of key targets such as SESN1, PRKAA2, and PPARGC1A, activating the AMPK signaling pathway, promoting acylcarnitine production and fatty acid β oxidation, improving cardiac lipid metabolism, and alleviating myocardial injury. The study partially reveals the biological connotations of TP in "broadening the chest and resolving masses as well as resolving phlegm and freeing channels".

The objective of this study was to examine the effect of rosehip ( Rosa rugosa Thunb.) ethanol extract (RRE) on liver fibrosis in mice and the underlying molecular mechanisms. RRE has no acute oral toxicity, and the MTD in mice is 46.14 g/kg. Histopathological analysis showed that RRE significantly ameliorated inflammation, necrosis, and apoptosis of hepatocytes and collagen deposition caused by CCl4. Further assays indicated that RRE significantly suppressed the production of MDA while markedly increasing the levels of SOD and GSH in the liver. The AST, ALT, IL-6, IL-1 beta, TNF-alpha, HA, LN, PCIII, and IVC levels in serum were decreased by RRE. Transcriptome analysis shows that RRE significantly upregulates the PPAR signaling pathway. The RT-q PCR results further confirmed the RRE up-regulating Ppar gamma, Rxr alpha, and Plin5 in the PPAR signaling pathway. The Western blot and immunohistochemical results indicate that RRE upregulated PPAR gamma, RXR alpha, and Perilipin 5 while down- regulating alpha-SMA and COL1A1 expression. The results indicate that RRE can ameliorate liver fibrosis in mice by upregulating the PPAR signaling pathway.

The Cortex Juglandis Mandshuricae (CJM) has the efficacy of penetrating the liver meridian, removing heat and dampness, and alleviating the liver, which corresponds to the pathogenesis of alcoholic fatty liver disease (AFLD) with damp heat accumulation. Modern research has shown that total flavonoids from Cortex Juglandis Mandshuricae (TFC) have hepatoprotective, antioxidant and antitumour pharmacological effects. However, there is no any investigation on the mechanism of TFC improving AFLD. In this work, a valid strategy combining UPLC-Q-Exactive Orbitrap-MS, network pharmacology and in vitro cellular experimental validation is proposed to predict the targets and pathways of TFC to ameliorate AFLD and to explore its mechanism of action. As a result, 26 flavonoids and 182 targets linked to TFC and AFLD were identified. These compounds realize their critical targets via various signaling pathways and perform multiple biological functions on the basis of the constructed compound-disease target networks. In vitro experiments demonstrated TFC had a protective impact on ethanol-treated L02 cells to a certain extent and could diminished lipid accretion. In addition, RT-qPCR and western blot results illustrated that TFC could regulate the expression of PPARα, CPT-1, SREBP-1c and FAS, and inhibit alcohol-induced lipid accumulation in L02 cells thereby alleviating AFLD. The present study further provides experimental justification for TFC to ameliorate AFLD in practical applications.

This study aims to investigate the effects of Gualou Xiebai Banxia Decoction(GXBD)on type 2 diabetes mellitus(T2DM)combined with acute myocardial infarction(AMI)in rats via chemerin/chemokine-like receptor 1(CMKLR1)/peroxisome proliferator-activated receptor α(PPARα)signaling pathway,and to explore the mechanism of GXBD in alleviating glucose and lipid metabolism disorders.The SD rats were randomized into control,model,positive control,and low-and high-dose GXBD groups.The rat model of T2DM was established by administration with high-fat emulsion(HFE)by gavage and intraperitoneal injection with streptozotocin,and then coronary artery ligation was performed to induce AMI.The control and model groups were administrated with the equal volume of normal saline,and other groups were administrated with corresponding drugs by gavage.Changes in relevant metabolic indicators were assessed by ELISA and biochemical assays,and the protein levels of chemerin,CMKLR1,and PPARα in the liver,abdominal fat,and heart were determined by Western blot.The results showed that GXBD alleviated the myocardial damage and reduced the levels of blood lipids,myocardial enzymes,and inflammatory cytokines,while it did not lead to significant changes in blood glucose.Compared with the model group,GXBD down-regulated the expression of chemerin in peripheral blood and up-regulated the expression of cyclic adenosine monophosphate(cAMP)and protein kinase A(PKA)in the liver.After treatment with GXBD,the protein levels of chemerin and CMKLR1 in the liver,abdominal fat,and heart were down-regulated,while the protein levels of PPARα in the liver and abdominal fat were up-regulated.In conclusion,GXBD significantly ameliorated the disorders of glycolipid metabolism in the T2DM-AMI model by regulating the chemerin/CMKLR1/PPARα signaling pathway to exert a protective effect on the damaged myocardium.This study provides a theoretical basis for further clinical study of GXBD against T2DM-AMI and is a manifestation of TCM treatment of phlegm and turbidity causing obstruction at the protein level.

Ethnopharmacological relevance: The Gualou-Xiebai-Banxia decoction (GXBD), a classical traditional Chinese medicine (TCM) formula, has beneficial effects in turbid phlegm obstruction syndrome, a type of coronary heart disease (CHD). However, the underlying mechanism and effective constituents of GXBD remain elusive. Our previous studies have shown that the effective constituents of GXBD may be enriched in the n-butanol fraction (GXB-N) and water fraction (GXB-W), the targets of which remain unknown. Aim of the study: To investigate whether GXB-N and GXB-W protect myocardial cells (MCs) via fibroblast growth factor 21 (FGF21) signaling and, if so, to elucidate the underlying mechanisms. Furthermore, to investigate the targets of GXB-N and GXB-W as potential therapeutic targets for cardiovascular disease (CVD). Materials and methods: Cell viability and apoptosis were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl2H-tetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, respectively. The content of FGF21 in the medium was measured using enzyme-linked immunosorbent assay (ELISA). Protein expression was detected using immunofluorescence and western blotting. Results: Apoptosis increased markedly in MCs exposed to oxidized low density lipoprotein (ox-LDL) 100 mu g/mL, with increased expression of FGF21, FGFR1 and ss Klotho, phosphorylation of fibroblast receptor substrate 2 alpha (FRS2 alpha) was suppressed. Following incubation with GXB-N and GXB-W 200 mu g/mL, the expression of FGF21, FGFR1, and ss Klotho and the phosphorylation of FRS2 alpha were increased. Conclusion: Ox-LDL may inhibit the phosphorylation of FRS2 alpha, inducing considerable FGF21 resistance and resulting in MC apoptosis. GXB-N and GXB-W restored and enhanced FGF21 sensitivity in MCs, consequently rescuing cells from ox-LDL-induced apoptosis. The FGF21-FRS2 alpha signal pathway may be part action targets of these two effective fractions of GXBD.

A series of novel ferulic acid derivatives were designed and synthesized, and the twenty-one compounds were evaluated for their antiviral activities against Respiratory syncytial virus (RSV), herpes simplex virus type 1 (HSV-1), and enterovirus type 71 (EV71). These derivatives with the core structure of diphenyl acrylic acids had cis-trans isomers, which were confirmed by 1H NMR, HPLC, and UV-vis spectra for the first time. The A5 had a selective effect against RSV but no work on herpes simplex virus type 1 and enterovirus type 71, which showed a therapeutic index (TI) of 32 and was significantly better than ferulic acid. The A5 had no scavenging effect on free radicals, but the A2 as the degradation of A5 showed an obvious scavenging effect on DPPH· and ABTS+·. In addition, the A5 had no toxicity to endothelial cells and even showed a proliferative effect. Therefore, the A5 is worth further optimizing its structure as a lead compound and investigating the mechanism of inhibiting Respiratory syncytial virus.

近5年来,中药界学者共发现64种中药成分具有保护心肌缺血再灌注的作用,其中主要有苷类(23种)、黄酮类(18种)、生物碱(7种)、酚类(5种)、糖类(4种),以及菇、有机酸、氨基酸、儿茶素类等.这些成分主要通过扩张冠状动脉,抑制氧化应激,抑制炎症反应,抑制心肌细胞凋亡、自噬,增强线粒体能量代谢功能等机制发挥防治心肌缺血再灌注损伤的作用.参考文献93篇.

目的 比较瓜蒌薤白半夏汤(GXBD)不同提取部位对心肌缺血大鼠的保护作用,初步探寻该经典方剂干预"胸痹"的物质基础.方法 瓜蒌、薤白、法半夏的比例为5:2:2,95％乙醇加热回流提取3次,依次用石油醚、氯仿、醋酸乙酯、正丁醇及水进行萃取,得GXB1～GXB5部位;药渣水煎后得GXB6部位.Wistar大鼠结扎冠状动脉左前降支,制备急性心肌缺血(AMI)模型.采用多导生理记录仪监测大鼠心电图,并统计ST段抬高阳性率.心肌切片氧化三苯四氮唑(TTC)法染色后,采用图像分析处理系统测算心肌梗死率.生化试剂盒检测血清肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)的活性.采用AMI动物模型及心肌缺血诊断指标评价GXBD的6个部位干预AMI的药效,首先进行各部位各剂量的纵向比较,确定每个部位的最佳作用剂量;然后进行6个部位之间的横向比较,筛选出有效部位.最后,对有效部位的化学成分进行理化鉴定.结果 对于AMI模型大鼠,GXB4～GXB6均能够显著降低AMI大鼠的心电图ST段抬高阳性率、心肌梗死率及血清CK、CK-MB活性,其中GXB4作用最显著;而GXB1～GXB3虽然也显示出一定的缺血保护作用,但结果无显著性差异.GXB4～GXB6部位共有的化学成分为糖类、香豆素、苷类,GXB4特有的成分为甾体及萜类.结论 GXB4～GXB6部位对AMI有显著干预效果,GXB4效果最为显著;发挥AMI保护作用的物质可能是糖类、香豆素、苷类、甾体及萜类.

This study aims to explore the role of hyperlipidemia in the mobilization of bone marrow (BM) endothelial progenitor cells (EPCs) induced by acute myocardial ischemia (AMI). To establish the hyperlipidemia complicated with AMI (HL-AMI) model, SD rats were intragastrically administered the high-fat emulsion for 4 weeks. Then their left anterior descending arteries were ligated. Rats in each group were randomly subdivided into seven subgroups. During 1st ~ 7th day following AMI modeling, rats in 1st ~ 7th subgroups were selected to be phlebotomized from their celiac artery after being anesthetized by pentobarbitone in turn. The quantity of circulating EPCs (CEPCs) was detected by flow cytometry, the expression of VEGF, eNOS, NO, MMP-9 in myocardial tissue was analyzed by western blot, and their plasma level was assayed by ELISA. Dynamic curves were plotted using these data. Within 7 days following AMI, compared with the AMI rats, in the HL-AMI rats, the myocardial infarct size, the plasma activity of CK, CK-MB, and the collagen deposition all remained at the higher levels; meanwhile, these rats showed more significant decreases in the count of CEPCs, the plasma level of VEGF etc., and their expression in myocardial tissue (P < 0.05 or P < 0.01). Our study showed that hyperlipidemia may attenuate the mobilization of BM EPCs induced by AMI via VEGF/eNOS/NO/MMP-9 signal pathway, which might partly account for hyperlipidemia hampering the repairs of AMI-induced cardiac injury.

Gualou-Xiebai-Banxia decoction has a long history of medical use for treating cardiovascular diseases in China. In this study, we investigated the protective effect and underlying mechanisms GXB in type II diabetes with acute myocardial ischemia (T2DM-AMI) rats. We hypothesized that GXB may display its protective effect on T2DM-AMI by reducing endothelial progenitor cells (EPCs) apoptosisviaactivating PI3K (phosphatidyl inositol 3-kinase)/Akt (serine/threonine protein kinase B)/eNOS (endothelial nitric oxide synthase) signaling. Rats were challenged with a high-fat diet and intraperitoneal injection of streptozotocin to induce a model of type II diabetes mellitus (T2DM) and coronary ligation to induce acute myocardial infarction (AMI). Changes in metabolites were assessed via enzyme-linked immunoassay and biochemical examination. The number and apoptosis rate of EPCs in peripheral blood were detected by flow cytometry. Target mRNAs and proteins in EPCs were analyzed by RT-PCR and Western blot analysis. The results demonstrated that GXB treatment decreased T2DM-AMI-associated changes in plasma fasting blood glucose, muscular enzymes, and blood lipids, and reduced oxidative stress. Furthermore, EPC apoptosis was increased in T2DM-AMI rats and was associated with decreased mRNA and protein levels of PI3K, Akt, and eNOS compared to the controls. Conversely, T2DM-AMI rats treated with GXB exhibited more circulating EPCs and downregulated levels of cell apoptosis, combined with increased mRNA and protein levels of PI3K, Akt, and eNOS compared to those of untreated T2DM-AMI rats. Our study showed that GXB treatment mitigated EPC apoptosis and promoted PI3K/Akt/eNOS signaling in T2DM-AMI rats.

近五年来,共发现能改善胰岛素抵抗的中药活性成分35种.全面概述了这35种成分的来源、理化性质、分子结构.它们通过调控不同信号通路发挥改善胰岛素抵抗作用,机制主要包括抑制氧化应激、抵抗炎症反应、调控葡萄糖转运通路、促进脂肪酸分解.参考文献50篇.

目的:在前期研究的基础上,探究瓜蒌薤白半夏汤正丁醇部位对缺血缺氧的骨髓间充质干细胞(BMSCs)凋亡的保护作用及机制.方法:90％乙醇回流提取+正丁醇萃取法制备瓜蒌薤白半夏汤正丁醇部位,传统黄酒加水煎煮法制备该方总提取物.分离培养大鼠BMSCs,将细胞分为正常对照组、模型对照组、瓜蒌薤白半夏汤150 μg/mL组和瓜蒌薤白半夏汤正丁醇部位50 μg/mL组.造模组以无血清的培养液、缺氧气体(5％CO2+94％N2+1％O2)处理24 h诱导细胞凋亡.以相应药物处理细胞24 h.通过倒置相差显微镜观察细胞形态,MTT法检测细胞存活率,TUNEL法检测细胞凋亡率,免疫荧光、Western Blot检测BMSCs中磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(AKT)蛋白的表达位点及磷酸化水平,分析磷酸化/非磷酸化蛋白的比值.结果:与正常对照组相比,模型对照组BMSCs存活率显著降低、凋亡率显著升高,PI3K、AKT蛋白的表达及磷酸化水平显著降低(P＜0.01);与模型对照组相比瓜蒌薤白半夏汤正丁醇部位50 μg/mL、瓜蒌薤白半夏汤150 μg/mL均能显著提高细胞存活率,降低细胞凋亡率;同时显著上调细胞内PI3K、AKT蛋白表达及磷酸化水平;且瓜蒌薤白半夏汤正丁醇部位的上述作用均优于瓜蒌薤白半夏汤总提取物(P＜0.05或P＜0.01).结论:瓜蒌薤白半夏汤正丁醇部位可能通过激活PI3K/AKT信号通路,逆转缺血缺氧诱导的BMSCs凋亡,提高缺血缺氧状态下干细胞的生存率.这可能是该方祛痰散结功效的部分生物学机制.

目的:研究瓜蒌薤白半夏汤(GXB)对2型糖尿病合并急性心肌缺血(T2DM-AMI)大鼠造血干细胞(HSCs)的保护作用机制.方法:雄性Wistar大鼠随机分为对照组、模型组、GXB组.通过灌服高脂乳剂+腹腔注射链脲佐菌素制备T2DM大鼠模型;将T2DM造模成功的大鼠进行冠脉结扎制造T2DM-AMI模型.流式细胞仪检测各组大鼠外周血HSCs含量;PCR和Western Blot检测心肌磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)、内皮型一氧化氮合酶(eNOS) mRNA和蛋白表达水平及被激活的程度(磷酸化/非磷酸化蛋白的比值).结果:模型组大鼠外周血HSCs凋亡率显著高于对照组(P＜0.01),而给予GXB后其凋亡率显著下调(P＜0.05),且GXB组HSCs数量显著高于模型组(P＜0.01).与模型组比较,GXB组大鼠心肌组织中PI3K、Akt和eNOS蛋白表达及其磷酸化水平、mRNA相对表达量显著提高(P＜0.05,P＜0.01).结论:GXB可能通过激活PI3K/Akt/eNOS信号通路发挥对T2DM-AMI模型大鼠HSCs的保护作用.

目的 研究瓜蒌皮提取物对缺血缺氧心肌细胞保护效果及抗氧化效果,初步探寻该药材防治心肌缺血的物质基础及作用机理.方法 采用水煎粗提法、水提醇沉法,制备瓜蒌皮水煎粗提物组、水提醇沉上清液组分.利用低氧气体、无血清培养液处理大鼠原代心肌细胞,制备缺血缺氧损伤模型.以注射用丹参粉针(Sal)为阳性对照药物,培养液中添加上述提取物培养细胞.倒置相差显微镜观察细胞形态变化,比色法(MTT)测其存活率,生化试剂盒检测细胞总抗氧化能力(T-AOC)以及总自由基/总超氧化物的含量.结果 瓜蒌皮水煎粗提物组(TP-T)、水提醇沉上清液组分(TP-1)能够剂量依赖地显著提高缺血缺氧细胞的存活率,并可显著提高细胞的总抗氧化能力,明显增强细胞清除自由基的活性,其中TP-1效果更优(P＜0.05).结论 瓜蒌皮水煎粗提物及水提醇沉上清液组分对缺血缺氧的心肌细胞均有显著保护作用,TP-1组分效果更好.该保护作用与这些组分的抗氧化能力密切相关.

近五年共发现37种中药活性成分具有调节脂蛋白代谢的作用.这些成分分别通过改善胰岛素抵抗、抑制炎症反应、调节氧化应激、调节脂蛋白代谢相关酶活性和基因表达等途径发挥作用.目前,对这些活性成分作用点、作用环节的探索仍处于起步阶段,因此,探索中药活性成分调节脂蛋白代谢的作用靶点及相互作用将成为今后研究的重点.

According to traditional Chinese medicine, lily bulb and Rehmannia decoction (LBRD) is a specialized formula for the treatment of "lily disease", the symptoms of which resemble the clinical manifestations of major depression. However, the molecular basis of the antidepressant mechanism of LBRD and the quality marker ingredients of LBRD remain unclear. This study aimed to investigate the quality marker ingredients of LBRD and to show the molecular mechanism of its antidepressant activities. In this study, we adopted the chronic unpredicted mild stress paradigm to construct a depression model. High-performance liquid chromatography (HPLC) was used to determine the levels of the main markers in LBRD. The underlying mechanism of LBRD was explored by measuring neurotransmitter and cytokine levels using enzyme-linked immunosorbent assay, and by quantifying differentially expressed gene (DEG) of transcriptome in the medial prefrontal cortex (mPFC) tissue through RNA sequencing. HPLC results showed that the average levels of quality marker ingredients of LBRD (ferulic acid, dioscin, verbascoside and catalpol) were 0.00079%, 0.00039%, 0.7% and 1.6% (w/w), respectively. LBRD intervention significantly attenuated the depressive phenotype compared with that in the depressed group. LBRD treatment altered the enriched DEGs in the signaling pathways of γ-aminobutyric acid (GABA) and glutamate neurotransmitter, synaptic plasticity and axon guidance, circadian rhythm and neural-immunity. GABAergic and glutamatergic synapses as well as brain-derived neurotrophic factor (BDNF)/TrkB-dependent phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin-1 (mTOR1), might be the main signaling pathways underlying the multi-target therapeutic effects of LBRD against depression.